Annals of Oncology 16 (Supplement 1): i64 – i65, 2005
doi:10.1093/annonc/mdi834
ESMO Minimum Clinical Recommendations for diagnosis,
treatment and follow-up of malignant glioma
Incidence
. The incidence of malignant glioma is 5– 7/100 000. Malig-
nant glioma may develop at all ages, the peak incidence
being in the fifth and sixth decades of life.
Diagnosis
. Malignant glioma comprises glioblastoma multiforme
(WHO grade IV), anaplastic astrocytoma (WHO grade III),
mixed anaplastic oligoastrocytoma (WHO grade III), and
anaplastic oligodendroglioma (WHO grade III). Diagnosis
after biopsy or tumor resection is made according to the
revised WHO classification.
Staging and risk assessment
. Staging includes imaging of the brain, ideally with MRI. If
repeat imaging is deemed necessary to determine residual
disease, it should be done within 24– 48 h after surgery.
Lumbar puncture is generally not necessary and staging of
other organs is not needed.
. Other than tumor grade, good performance status and an
intact neurological function, tumor resection, and age <50
years have been identified as more favorable prognostic
factors.
. Prognosis depends on tumor grade. Glioblastoma carry the
worst prognosis, while pure oligodendroglioma tend to have
a better outcome and improved response to therapy. Mixed
anaplastic oligoastrocytoma behave similarly to anaplastic
astrocytoma with an intermediate prognosis.
Treatment plan
. Patients should be evaluated by a specialized multidisciplin-
ary team. Special consideration needs to be given to per-
formance status and neurological function.
Newly-diagnosed patients
. Surgery is commonly the initial therapeutic approach for
debulking and obtaining tissue for diagnosis. Tumor resec-
tion is of prognostic value, but attempting maximal tumor
resection remains controversial [IV, C]. Implantation of che-
motherapy-impregnated wafer (BCNU-polymer) into the
resection cavity has shown only a marginal benefit [II, B].
. Fractionated focal radiotherapy (60 Gy, 2 Gy 30; or equiv-
alent doses/fractionations) is the standard treatment after
q 2005 European Society for Medical Oncology
resection or biopsy [I, A]. Escalating doses beyond 60 Gy
has not been shown of value. In elderly patients or patients
with a low performance status shorter hypofractionated regi-
mens (e.g. 3 Gy 10) are commonly proposed.
. Adjuvant chemotherapy with procarbazine, lomustine
(CCNU) and vincristine (PCV regimen) has failed to
improve survival in prospective randomized studies [I, A].
Nevertheless, based on a large meta-analysis [III, B] nitro-
sourea-based chemotherapy may improve survival in
selected patients.
. Concomitant and adjuvant temozolomide chemotherapy has
demonstrated to significantly improve median and 2-year
survival in a large randomized trial [I, A]. Selecting patients
likely to benefit from therapy based on MGMT gene methyl-
ation has been suggested [II, B].
Recurrent disease
. Some benefit of chemotherapy has been shown for patients
with an adequate performance status who have not received
prior adjuvant cytotoxic therapy. Anaplastic astrocytomas
are more likely to respond to chemotherapy than glioblas-
toma. [III, B].
. Repeat surgery and implantation of chemotherapy-impreg-
nated polymers may prolong survival in selected patients
[II, B].
Oligodendroglioma
. Oligodendroglioma carry a somewhat better prognosis. In
particular the subgroup of patients with a deletion on
chromosome 1p and 19q seem to have a longer survival and
better response to chemotherapy. However, at the current
time 1p/19q LOH determination should not be routinely per-
formed and should not influence the initial treatment rec-
ommendations. In patients with recurrent oligodendroglioma,
chemotherapy should be considered [II, B].
Response evaluation
. If response is evaluated, it should be done with MRI. Con-
trast enhancement and presumed tumor progression on ima-
ging 4–8 weeks after the end of radiotherapy may be an
imaging artifact due to changes in the blood-brain barrier
permeability and should be confirmed 4 weeks later with a
second MRI.
. Response to chemotherapy is evaluated according to the
WHO criteria, but should also include an assessment of the
neurological function and corticosteroid use (Macdonald
criteria).

Follow-up
. Follow-up consists of a clinical evaluation with particular
attention to neurological function, seizures or seizure
equivalents and corticosteroid use. Patients should be
tapered off steroid use as early as possible.
. Laboratory tests are not indicated unless patient is receiving
chemotherapy (blood counts), corticosteroids (glucose) or
anti-epileptic drugs (blood counts, liver function tests).
Note
Levels of Evidence [I –V] and Grades of Recommendation
[A –D] as used by the American Society of Clinical Oncology
are given in square brackets. Statements without grading were
considered justified standard clinical practice by the expert
authors and the ESMO faculty.
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Coordinating authors for the ESMO Guidelines Task Force: R. Stupp1,
N. Pavlidis2 & S. Jelic3
1
Invited author, University Hospital (CHUV), Multidisciplinary Oncology
Center, 1011 Lausanne, Switzerland; 2Assigned task force member,
University of Ioannina, Dept. Medical Oncology, 45 110 Ioannina,
Greece; 3Assigned task force member, Institute of Oncology and
Radiology of Serbia, Department of Medical Oncology, Pasterova 14,
11000 Belgrade, Serbia
Approved by the ESMO Guidelines Task Force: December 2004.
Correspondence to:
ESMO Guidelines Task Force
ESMO Head Office
Via La Santa 7
CH-6962 Lugano
Switzerland